Day: 01/03/2023

GLP-1 receptor agonist use for more than 1 year may increase thyroid cancer risk

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Adults with type 2 diabetes who use a GLP-1 receptor agonist for more than 1 year may have an increased risk for thyroid cancer, according to findings published in Diabetes Care.

“Our results suggest that thyroid cancer risk should be considered with GLP-1 receptor agonists, particularly in patients treated for 1 to 3 years,” Jean-Luc Faillie, MD, PhD, professor and head of the department of medical pharmacology and toxicology at Montpellier University Hospital and University of Montpellier in France, and colleagues wrote. “Complementary pharmacovigilance analysis with use of the worldwide adverse drug reactions database provided consistent results.”

Risk for thyroid cancer among adults with type 2 diabetes using GLP-1 receptor agonists
Data were derived from Bezin J, et al. Diabetes Care. 2022;doi:10.2337/dc22-1148.

Researchers conducted a case-control analysis of data from France’s national health care insurance system database. People with type 2 diabetes using GLP-1 receptor agonists, DPP-IV inhibitors or multiple therapies combining metformin, sulfonylureas, repaglinide, alpha-glucosidase inhibitors or thiazolidinediones from 2006 to 2018 were included. Researchers obtained incident cases of thyroid cancer from 2014 to 2018 through hospital diagnoses and medical procedures associated with thyroid cancer. People with thyroid cancer were matched with up to 20 control participants without thyroid cancer by age, sex and diabetes duration. A lag time of 6 months before cancer diagnosis was used to reduce the risk of reverse causation. Researchers identified adults who used GLP-1 receptor agonists and DPP-IV inhibitors and obtained the duration of use in the 6 years before the lag time.

The study included 3,746,672 people with type 2 diabetes, of whom 4,466 developed thyroid cancer. After excluding those with a history of cancer, researchers analyzed data from 2,562 adults with thyroid cancer and 45,184 matched controls without thyroid cancer.

Before the lag time, 12% of the thyroid cancer group and 9.6% of the control group used GLP-1 receptor agonists, with more than 80% in both groups using liraglutide (Victoza, Novo Nordisk). Those currently using a GLP-1 receptor agonist had a higher risk for thyroid cancer compared with those not currently using the medication (adjusted HR = 1.46; 95% CI, 1.23-1.74). Those who used a GLP-1 receptor agonist for 1 to 3 years (aHR = 1.58; 95% CI, 1.27-1.95) or more than 3 years (aHR = 1.36; 95% CI, 1.05-1.74) also had a higher risk for thyroid cancer than non-users.

Adults using DPP-IV inhibitors for more than 3 years had an increased risk for thyroid cancer compared with nonusers (aHR = 1.19; 95% CI, 1.04-1.35), but no other significant associations with the drug class were observed.

Researchers also conducted an analysis using data from the WHO’s pharmacovigilance database from April 28, 2005, to March 1, 2021. Data were collected to estimate associations between GLP-1 receptor agonist use and the risk of differential reporting of thyroid cancer compared with other diabetes drugs, excluding insulin. Associations were estimated using proportional reporting ratio.

In the analysis, 606 spontaneous reports of thyroid cancer with GLP-1 receptor agonist use were found. Disproportionate reporting of any thyroid cancer (proportional reporting ratio, 30.5; 95% CI, 25.1-37.2) and medullary thyroid cancer (proportional reporting ratio, 28.7; 95% CI, 16.1-51.1) were observed with GLP-1 receptor agonist use.

“Clinicians should be aware of this potential risk [for thyroid cancer] in initiating a GLP-1 receptor agonist and carefully monitor exposed patients, especially in the presence of other risk factors for thyroid cancer,” the researchers wrote.

Small airways disease may persist for many with long COVID

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Small airways disease was common in patients with persistent symptoms following COVID-19, independent of severity of initial infection, according to a single-center study published in Radiology.

“For the first time, we’re describing small airways disease in this population of COVID-19 patients with persistent symptoms,”Alejandro P. Comellas, MD, professor of internal medicine and faculty in thedivision of pulmonary, critical care and occupational medicine at Carver College of Medicine at the University of Iowa, Iowa City, said in a related press release. “Something is going on in the distal airways related to either inflammation or fibrosis that is giving us a signal of air trapping.”

Lungs
Source: Adobe Stock.

The single-center study included 100 participants (median age, 48 years; 66% women) with post-acute sequelae of COVID-19 for at least 30 days enrolled from June to December 2020 and 106 matched healthy participants enrolled from March to August 2018. Those with post-acute sequelae of COVID-19, or long COVID, were categorized based on the highest level of acute care received: ambulatory (67%), hospitalized (17%) or requiring ICU care (16%). Researchers collected symptoms, pulmonary function tests and chest CT images, and performed inspiratory CT after inhalation and evaluated post-exhalation expiratory scans to assess air trapping and compare the two groups.

The mean percent of total lung classified as ground glass opacities was 3.7% in the ambulatory group compared with 13.2% in the hospitalized group and 28.7% in the ICU group (P < .001 for both comparisons).

The mean percentage of total lung affected by air trapping was 25.4% in the ambulatory group, 34.6% in the hospitalized group and 27.3% in the ICU group compared with 7.2% among healthy participants (P < .001). This air trapping persisted among eight of nine participants who underwent imaging more than 200 days after diagnosis.

Quantitative analysis of expiratory chest CT images, performed with supervised machine learning, showed evidence of small airways disease, according to the release.

Median time from diagnosis to chest CT imaging was about 75 days. The researchers noted that persistence of respiratory abnormalities in this period raises concern for permanent airway remodeling and fibrosis following SARS-CoV-2 infection, according to the release.

“There is some disease happening in the small airways independent of the severity of COVID-19,” Comellas said in the release. “We need to investigate further to see whether it is transient or more permanent.”

The researchers plan to follow the patients to evaluate how many improve and how many remain with abnormal findings.

“If a portion of patients continues to have small airways disease, then we need to think about the mechanisms behind it,” Comellas said in the release. “It could be something related to inflammation that’s reversible, or it may be something related to a scar that is irreversible, and then we need to look at ways to prevent further progression of the disease.”

Brett M. Elicker, MD, clinical professor in the department of radiology and biomedical imaging at the University of California, San Francisco, discussed the findings in an accompanying editorial in Radiology. Elicker said “it is important to note that not all pulmonary fibrosis … is permanent. … Regardless of the imaging findings, the most important question is whether the airway obstruction and post-[organizing pneumonia]/[diffuse alveolar damage] fibrosis contribute to persistent symptoms after COVID-19 infection with the contribution of airways disease higher in the outpatients, and the contribution of OP/DAD greater in the patients admitted to ICU. Longer-term studies assessing the clinical and imaging manifestations 1-2 years after the initial infection are needed to fully ascertain the permanent manifestations of post-COVID fibrosis.”

Air pollution raises mortality risk, worsens lung function in fibrotic ILD

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In patients with fibrotic interstitial lung disease, exposure to small particulate matter was linked to increased mortality, poor lung function and faster disease progression, according to a study in JAMA Internal Medicine.

Further, sulfate, ammonium and nitrate elements in the air — which researchers called byproducts of industrial and transportation activities — had the worst harm on this patient population, according to researchers.

Air Pollution from stacks
In every cohort, researchers found that higher exposure to sulfate, ammonium and nitrate PM2.5 elements in particular were linked to worse baseline lung function and a higher risk for mortality. Source: Adobe Stock

Gillian C. Goobie

“The majority of studies of [particulate matter 2.5 m or less in diameter (PM2.5)] health effects have not evaluated the impact of PM2.5 composition on outcomes,” Gillian C. Goobie, MD, PhD, FRCPC, who just completed her PhD in the department of human genetics at the University of Pittsburgh School of Public Health, told Healio. “This work indicates that composition matters to a substantial degree in this vulnerable population of patients with fibrotic interstitial lung disease, highlighting the need to investigate compositional associations in other chronic disease and general populations. These findings may influence future policy and regulatory interventions to mitigate the harmful impacts of human-derived sources of pollution.”

In a multicenter, international, prospective cohort study, Goobie and colleagues evaluated 6,683 adults (55% men; median age, 66 years; range, 58-73; 84% white; 6.5% Asian; 3.1% Black) with fibrotic ILD from three registries — Simmons Center for Interstitial Lung Disease Registry at the University of Pittsburgh, the Pulmonary Fibrosis Foundation Registry and the Canadian Registry for Pulmonary Fibrosis — between June 1, 2021, and Aug. 2, 2022. Researchers aimed to observe how PM2.5 exposure was related to mortality and lung function. In order to observe associations of PM2.5 exposures of 8 m/m3 or greater in the 5 years prior to censoring (ie, before death, lung transplant or cessation of follow-up), researchers used multivariable Cox models for mortality and linear mixed models for lung function.

Median follow-up was 2.9 years, during which 28% of the population died and 10% underwent lung transplant.

According to researchers, increased mortality with a PM2.5 exposure of 8 m/m3 or higher was observed in all three cohorts but varied in each location. Specifically, for those in the Simmons cohort, the hazard ratio for mortality was 4.4 (95% CI, 3.51-5.51); in the Pulmonary Fibrosis Foundation cohort, the hazard ratio was 1.71 (95% CI, 1.32-2.21); and in the Canadian Registry for Pulmonary Fibrosis cohort, the hazard ratio was 1.45 (95% CI, 1.18-1.79).

Goobie told Healio this was initially a surprising finding before they found that differences in patient exposures to human-derived sources of PM2.5 explained the variability.

“We found that patients in our Simmons cohort, who are primarily recruited from Western Pennsylvania, exposed to high PM2.5 (above the 8 g/m3 American Thoracic Society annual recommended threshold for exposure) had approximately 440% increased risk of death as compared to their counterparts with annual exposures less than 8 g/m3,” Goobie said. “In contrast, the mortality risk was only approximately 45% higher for the high-exposure group in our Canadian cohort as compared to the low-exposure group. Our Western Pennsylvania patients were exposed to much higher levels of these anthropogenic PM2.5 pollutants, and these pollutants seemed to be driving the greater mortality impact.”

In every cohort, researchers found that higher exposure to sulfate, ammonium and nitrate PM2.5 elements in particular were linked to worse baseline lung function and a higher risk for mortality, with ammonium (HR = 50.99; 95% CI, 2.46-1,056.64) and nitrate (HR = 3.78; 95% CI, 2.3-6.2) showing increased risk for mortality by meta-analysis.

Meta-analysis also showed sulfate, ammonium and nitrate to be linked to worsening lung function as demonstrated by decreasing rates of both FVC and diffusion capacity of carbon monoxide.

According to Goobie, these results indicate that clinicians need to talk about the significance of air quality with their patients.

“It is important to know about what levels of exposures an individual may have accumulated throughout their lifetime and what their exposure risk is now,” Goobie said. “Clinicians should be helping to provide their patients with the tools and resources they need to monitor air quality where they live. We should be teaching our patients about how to modify their behavior during poor air quality days (ie, exercising indoors rather than outdoors, keeping windows closed). We should also be acting as partners to our patients in advocating for cleaner air and better environmental policies that protect the health and well-being of all people.”

“Without [the contributions of the patients from each of the registry studies], we would not be on this path to finding a cure for pulmonary fibrosis or making the quality of the air safer for everyone to breathe,” Goobie added.

Exposure to solid fuel for cooking linked to lung cancer mortality risk

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Exposure to household air pollutants, especially solid fuel, appeared linked to lung cancer death among individuals who have never smoked, according to a study published in American Journal of Respiratory and Critical Care Medicine.

Elvin S. Cheng

“Since lung cancer patients can present with a wide range of clinical symptoms before a proper diagnosis is made, ranging from asymptomatic, some common chest symptoms (eg, cough or hemoptysis) or systemic symptoms (eg, lethargy or weight loss), to atypical presentations often due to metastasis, it remains a challenge for clinicians to make a timelier diagnosis,” Elvin S. Cheng, PhD, MPH, BScMed, MBBS, research scientist from the Daffodil Centre at the University of Sydney, told Healio. “As early detection would allow better prospect of curative treatments, a clinical history of strong exposure to solid fuels could be considered as one of the criteria for early diagnostic or screening intervention (using low-dose CT scan) for lung cancer in the never-smoking populations.”

Cooking fuel
Researchers observed that the most frequently reported household air pollutant was solid fuel use for cooking at 67%. Source: Adobe Stock

In a prospective cohort study, Cheng and colleagues analyzed 323,794 individuals (mean age, 51.5 years; 89% women) who never smoked from the China Kadoorie Biobank between 2004 and 2008, to determine if household air pollution and secondhand tobacco smoking were related to death due to lung cancer.

Researchers used participants’ reports of domestic fuel use — including whether they used gas, coal, wood, electricity or other fuel and how often — to calculate the total time of household air pollution exposure. They assessed secondhand smoke exposure according to the participants’ exposure at home, the workplace or in public.

In order to find associations, researchers used Cox regression and adjusted for confounders.

Of the total cohort, 84.8% reported ever exposure to household air pollutants and 91% reported ever exposure to secondhand smoke, with 78.2% exposed to both and 2.4% to neither.

Researchers additionally observed that the most frequently reported household air pollutant was solid fuel use for cooking at 67%, followed by a “coal-smoky home” at 27%, which researchers defined as visible or smellable air pollution from use of coal burning for heating.

Individuals were studied until Dec. 31, 2016, with a median follow-up of 10.2 years. In that time, 979 individuals from the cohort died of lung cancer.

Although researchers did not find a significant association between household air pollution ever exposure and lung cancer mortality, they did find a significant log-linear positive relationship between cumulative duration of exposure and lung cancer death. Researchers observed that per every 5-year increment of exposure duration, risk for death due to lung cancer increased by 4% (HR = 1.04; 95% CI, 1.01-1.06).

Researchers also found that the highest risk for lung cancer mortality occurred among individuals who experienced 40.1 years to 50 years of exposure to household air pollution (HR = 1.53; 95% CI, 1.13-2.07). The hazard ratio for individuals who experienced more than 50 years of exposure was 1.27 (95% CI, 0.93-1.73).

Peter Ka Hung Chan

The latter hazard ratio was likely lower due to survivor bias, as people who used solid fuels for a long time tended to be elderly but healthy enough to survive without major disease, according to study researcherPeter Ka Hung Chan, DPhil, MSc, BSc, research fellow from the Oxford British Heart Foundation Centre of Research Excellence at the University of Oxford.

“Elderly who were already affected by the exposure would have a lower chance of being included in the study,” Chan told Healio.

When looking at individual factors such as sex, age, area (urban vs. rural), past history of respiratory disease and self-rated poor health in subgroup analysis of household air pollution exposure and lung cancer death, researchers observed no significant differences between the groups, except for a borderline significant difference between “poor” health (HR = 0.97; 95% CI, 0.91-1.04) and “not poor” health (HR = 1.05; 95% CI, 1.02-1.08; P for heterogeneity = .047).

In terms of secondhand tobacco smoking and lung cancer mortality, researchers found no significant association between the two factors, which Chan said is “consistent with the more recent prospective studies (as opposed to earlier retrospective studies).”

“We need more large prospective studies with more accurate assessment of solid fuel use and secondhand smoke exposure, examining not only risk of lung cancer death but also risk of developing newly diagnosed lung cancer,” Chan told Healio. “For example, we could combine questionnaire data with direct measurement of harmful chemicals in solid fuel and secondhand smoke within a prospective study, so we can potentially tease out the specific pollutants that are most relevant to lung cancer risk.”

The populations in most developed countries have seen an increase in the proportion of never-smokers due to stringent tobacco control, according to Cheng.

“However, the etiology of lung cancer among never-smokers is still largely unknown,” Cheng told Healio. “Research to study the major risk factors for lung cancer unrelated to tobacco smoke is greatly warranted to combat the impact of lung cancer as the leading cause of cancer mortality globally.”

Chan also told Healio about how these findings impact clinicians.

“Generally, I’d hope clinicians advise their patients to avoid solid fuel or secondhand smoke — eg, don’t stay too close to a barbecue for too long,” Chan said. “Often patients would get respiratory symptoms well before any other respiratory diseases like lung cancer, and those are warning signals about the potential harm on their lungs.”

This study by Cheng and colleagues adds to the literature indicating that exposure to household air pollutants needs to be studied further and global organizations need to take action on this issue to improve public health, according to an accompanying editorial byOm P. Kurmi, PhD, associate professor in epidemiology and health care research at Coventry University, U.K.

“It is too early to understand the full spectrum of diseases associated with exposure to HAP,” Kurmi wrote. “Some of these large, prospective cohorts have tried to provide better estimates; however, they often have raised some serious public health concerns, which suggests that we need to develop policies for prevention rather than waiting to understand the full spectrum of diseases and mechanisms of how some of the HAP and SHS act. Cardiorespiratory diseases and lung cancer control should be targeted to improve global health. This is important if we are serious about reducing one-third of premature mortality from noncommunicable diseases by 2030, one of the key goals of the United Nations Sustainable Development Goals.”

55% of patients have persistent symptoms 2 years after COVID-19 infection

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More than half of patients who were hospitalized with COVID-19 reported at least one persistent symptom 2 years post-infection, regardless of initial disease severity, researchers reported.

The most frequently reported symptoms at 2 years were fatigue and muscle weakness.

Proportion of COVID-19 survivors with at least one persistent symptom
Data were derived from Huang L, et al. Lancet Respir Med. 2022;doi:10.1016/S2213-2600(22)00126-6.

“Several cohort studies have highlighted that the health effects of COVID-19 could persist up to 1 year after acute infection, most of which had no control groups of individuals who had not contracted COVID-19 and focused only on symptomatic sequelae or respiratory outcomes,”Lixue Huang, MD, from the department of pulmonary and critical care medicine at China-Japan Friendship Hospital at Capital Medical University and the National Center for Respiratory Medicine at the National Clinical Research Center for Respiratory Diseases, Beijing, and colleagues wrote in The Lancet Respiratory Medicine. “Hence, long-term and overall health outcomes of COVID-19 are largely unknown.”

Huang and colleagues reported 2-year follow-up data from an ambidirectional, longitudinal cohort study of 1,192 patients (median age, 57 years; 46% women) who survived COVID-19 and were discharged from Jin Yin-tan Hospital between January and May 2020. Participants completed three follow-up assessments during which the researchers measured health outcomes at 6 months, 12 months and 24 months after COVID-19 symptom onset using 6-minute walking distance, laboratory tests and questionnaires about symptoms, mental health, health-related quality of life, return to work and health care use after discharge. Also included in this study were participants without COVID-19 who were age-, sex- and comorbidities-matched to determine COVID-19 survivor recovery status at 2 years.

Median follow-up after COVID-19 symptom onset was 185 days for the 6-month visit, 349 days for the 12-month visit and 685 days for the 24-month visit.

The proportion of COVID-19 survivors with at least one reported symptom declined from 68% at 6 months to 55% at 2 years (P < .0001). Fatigue or muscle weakness was the most frequently reported symptom, present in 52% of patients at 6 months.

Compared with 26% of patients with a modified British Medical Research Council (mMRC) score of at least 1 at 6 months, 14% of patients had a score of at least 1 at 2 years (P < .0001).

Researchers reported improvement in health-related quality of life in nearly all domains, especially anxiety or depression. The proportion of patients with symptoms of anxiety or depression decreased from 23% at 6 months to 12% at 2 years (P < .0001). The researchers reported a continual decline in the proportion of patients with a 6-minute walking distance less than the lower limit of normal overall and in subgroups of different initial disease severity, with 89% of 494 COVID-19 survivors returning to their original work at 2 years.

Those with long COVID symptoms at 2 years reported more mobility problems (OR = 3.81; 95% CI, 1.62-8.93), more pain or discomfort (OR = 4.42; 95% CI, 3.14-6.21) and more anxiety or depression (OR = 7.46; 95% CI, 4.12-13.52) compared with survivors without long COVID. COVID-19 survivors also reported more problems with usual activity (2% vs. < 1%), more pain or discomfort (23% vs. 5%) and anxiety or depression (12% vs. 5%) at 2 years compared with controls.

Finally, researchers observed a higher proportion of COVID-19 survivors who received higher-level respiratory support during hospitalization with lung diffusion impairment (65% vs. 36%; P = .0009), reduced residual volume (62% vs. 20%; P < .0001) and total lung capacity (39% vs. 6%; P < .0001) compared with controls.

“The COVID-19 survivors had not returned to the same health status as the general population 2 years after acute infection, so ongoing follow-up is needed to characterize the protracted natural history of long COVID; we plan to conduct yearly follow-ups in this cohort,” the researchers wrote. “The value of rehabilitation programs in mitigating the effects of long COVID and in accelerating recovery requires further exploration.”

Vaping, cannabis use increasing among US teens

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The increasing use of cannabis and vaping among U.S. adolescents may be associated with how teens spend their time, according to a study published in Substance Use & Misuse.

Specifically, several factors, such as social engagement, participation in structured activities, level of adult supervision and paid employment, correlated with substance use overall.

Marijuana leaf

Using data from 536,291 adolescents in the Monitoring the Future Study gathered through annual, nationally-representative surveys from 1991 to 2019, Noah T. Kreski, MPH, data analyst for Columbia University Mailman School of Public Health, and colleagues analyzed trends in use of cigarettes, alcohol, cannabis, other substances and vaping of nicotine for those in grades eight, 10 and 12. They then categorized respondents into six groups based on amounts of social time, level of engagement in organized activities, paid employment and, for those with high social time and high engagement, whether activities were more supervised, such as sports, or less supervised, such as dating or parties.

Noah T. Kreski

“We had seen such strong patterning of internalizing symptoms (like depressive symptoms and low self-esteem) based on how young people spend their time [in our previous research]. Extending that work to substance use seemed like a natural next step,” Kreski told Healio.

Substance use tied to time use patterns

Study results revealed declines across decades for most substance use outcomes, including alcohol, cigarette and other substance use, with the largest decreases noted among groups with significant paid employment or high levels of social time, either with low engagement in other activities or lower levels of supervision. Notably, initial prevalence of substance use was highest in these groups. Conversely, the smallest decreases were observed among groups with low levels of peer socialization, although these groups had very low prevalence of substance use in general, according to the researchers.

Despite decreases in substance use over time, cannabis use increased, with the smallest increase seen in the group with low levels of social time and low engagement in organized activities and the largest increase seen in the paid employment group.

Vaping, for which data were available from 2017 onward, also substantially increased during the study period. The largest increase in nicotine vaping occurred among adolescents in the highly social and engaged group with less supervision. In contrast, the largest increase in cannabis vaping occurred among those who were highly social but disengaged. Vaping of both substances was most prevalent in the highly social and engaged group with less supervision.

Substance use overall was lowest in the groups with low levels of social time and highest in the highly social and employed groups, according to the data.

“While some of the results aligned with expectations (like low supervision or high time with peers contributing to higher substance use), it was surprising to see that working a paid job was a risk factor for substance use as well. While the pathways are unclear, future research should look at this group more and provide support where needed,” Kreski said.

In terms of specific substance use, data also showed the following:

  • 15% of respondents reported any past 2-week binge drinking.
  • 27.4% reported drinking alcohol in the past month.
  • 14.7% reported smoking cigarettes in the past month.
  • 12.6% reported any past-month cannabis use.
  • 8.6% reported past-month use of other substances.
  • 12.3% reported nicotine vaping.
  • 6.2% reported cannabis vaping.

Importantly, these data perhaps indicate the need for greater public health measures, particularly those targeting vaping and cannabis use, the researchers noted.

“With how universal the rising trends are, parents should check in with their adolescents about substance use — not from a place of judgment or punishment but open discussion and support. Empowering all young people to make the best, informed choices they can while focusing interventions on cannabis and vaping is a great next step,” Kreski said.

Looking ahead

In the future, Kreski and colleagues are planning to evaluate how these time use patterns relate to externalizing symptoms, such as theft or fighting, but other areas, especially those that interest adolescents themselves, warrant further study.

“Apart from that, I’d love to encourage the development of a system where young people can directly provide feedback on the topics and problems that they find most important, what they think should be studied further. Research should always be guided by the population being studied, and empowering young people is incredibly important,” Kreski said.

Why does the dog wag its tail? It’s only a communication tool, doesn’t help in manoeuvres

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https://www.wionews.com/science/what-is-the-purpose-of-dogs-tail-study-shows-it-does-not-help-in-manoeuvres-but-only-a-communication-tool-548935